Moraxella (Branhamella) catarrhalis is a common and important human respiratory tract pathogen. It is the third most common bacterial cause of otitis media in children after Streptococcus pneumoniae and non- typeable Haemophilus influenzae. M. catarrhalis is also an important cause of lower respiratory tract infection in adults with chronic obstructive pulmonary disease (COPD). In view of the morbidity and cost associated with infections caused by M. catarrhalis, there is significant interest in developing vaccines to prevent these infections. During the previous funding Period, two outer membrane proteins (OMP CD and OMP E) with are potential vaccine antigens have been identified and initially characterized. The goal of the proposed studies is to more rigorous study OMP CD and E as potential vaccine antigens. Our hypothesis is that immunization with OMP CD and E will generate an immune response which will protect from infection cased by all strains of M. catarrhalis. Emphasis is placed on studying the human immune response because M. catarrhalis is an exclusively human pathogen. The proposal has four specific aims. In Aim 1, the degree of sequence conservation of OMP E among strains of M. catarrhalis will be characterized. In Aim 2, potentially protective (bactericidal) epitopes on OMP on CD and OMP E will be identified. In Aim 3, the human immune response to OMP CD and E and potentially protective determinants on OMPs CD and E will be studied in epidemiologically well defined samples from children and adults. Finally, in Aim 4, to study the human immune response to immunization with OMP CD and E, SCID mice reconstituted with human peripheral blood lymphocytes will be immunized and the immune responses will be characterized with regard to a) isotype and subclass distribution of antibodies, b) the establishment of a memory response, and c) the bactericidal activity of the antibodies. The proposed studies will generate information on the human immune response to OMP CD and E. This information will be important in assessing the feasibility of proceeding to the testing of OMP CD and E as vaccine antigens in humans to prevent infections caused by M. catarrhalis.